It's About Timing: Contrasting the Metabolic Effects of Early vs. Late Time-Restricted Eating in Humans.

PURPOSE OF REVIEW: Time-restricted eating (TRE), a form of intermittent fasting, restricts feeding time across the day, imposing a daily 'eating window'. The time of day when the eating window occurs could result in differential metabolic effects. Here, we describe recent intervention studies in humans assessing the metabolic consequences of an early- (i.e., eating window starting in the early morning) vs. late (i.e., eating window starting after midday)-TRE protocol. RECENT FINDINGS: Well-controlled studies indicate that both TRE protocols effectively reduce body weight and improve altered glucose metabolism, lipid profile, inflammation, or blood pressure levels. An early-TRE (e-TRE) might have a further positive impact on improving blood glucose, insulin levels, and insulin resistance. However, the studies directly assessing the metabolic consequences of an early- vs. late-TRE have shown dissimilar findings, and more well-controlled clinical trials are needed on the metabolic benefits of these two types of TRE. Evidence suggests that an e-TRE might have enhanced metabolic results, particularly regarding glucose homeostasis. More long-term studies, including larger sample sizes, are needed to assess the metabolic, circadian, and adherence benefits, together with socio-cultural acceptance of both TRE approaches.

Metabolic Effects of Brown Adipose Tissue Activity Due to Cold Exposure in Humans: A Systematic Review and Meta-Analysis of RCTs and Non-RCTs.

Brown adipose tissue (BAT), specialized in thermoregulation in mammals, has been linked to improved glucose and lipid homeostasis when activated by cold exposure (CE). This systematic review and meta-analysis assessed the metabolic effects of CE-induced BAT activation in healthy humans, examining changes in glucose and lipid metabolism compared to thermoneutrality (TN). A literature search was conducted, identifying relevant human studies, including randomized controlled trials (RCTs) and non-RCTs, based on predefined inclusion criteria. Seven studies (a total of 85 participants) fully met the criteria. Data on plasma glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) were extracted for meta-analysis. When comparing TN and CE under fasting conditions, there were no significant changes in glucose, insulin, or TG concentrations (all p > 0.36). In contrast, CE significantly increased FFA concentrations (p = 0.002; n = 38). Bias was absent for all parameters, but heterogeneity was observed for insulin (I2 = 74.8%). CE primarily affects FFA concentration, likely reflecting cold-induced BAT activity. This suggests that circulating FFAs, serving as the primary fuel for thermogenesis, could indicate BAT activation. However, understanding the effects of BAT activation on overall metabolism requires a broader approach beyond fasting glucose and lipid concentration measurements.

[Intermittent fasting and human metabolic health]. / El ayuno intermitente y sus efectos en la salud metabólica en humanos.

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

Effect of a pescetarian and vegan diet on fatty acid composition in blood and spermatozoa in young healthy men.

INTRODUCTION: There is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men. METHODS: Four groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content. RESULTS: Main findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group. CONCLUSION: Higher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men.

Late, but Not Early, Night Sleep Loss Compromises Neuroendocrine Appetite Regulation and the Desire for Food.

OBJECTIVE: There is evidence that reduced sleep duration increases hunger, appetite, and food intake, leading to metabolic diseases, such as type 2 diabetes and obesity. However, the impact of sleep timing, irrespective of its duration and on the regulation of hunger and appetite, is less clear. We aimed to evaluate the impact of sleep loss during the late vs. early part of the night on the regulation of hunger, appetite, and desire for food. METHODS: Fifteen normal-weight ([mean ± SEM] body-mass index: 23.3 ± 0.4 kg/m2) healthy men were studied in a randomized, balanced, crossover design, including two conditions of sleep loss, i.e., 4 h sleep during the first night-half ('late-night sleep loss'), 4 h sleep during the second night-half ('early-night sleep loss'), and a control condition with 8h sleep ('regular sleep'), respectively. Feelings of hunger and appetite were assessed through visual analogue scales, and plasma ghrelin and leptin were measured from blood samples taken before, during, and after night-time sleep. RESULTS: Ghrelin and feelings of hunger and appetite, as well as the desire for food, were increased after 'late-night sleep loss', but not 'early-night sleep loss', whereas leptin remained unaffected by the timing of sleep loss. CONCLUSIONS: Our data indicate that timing of sleep restriction modulates the effects of acute sleep loss on ghrelin and appetite regulation in healthy men. 'Late-night sleep loss' might be a risk factor for metabolic diseases, such as obesity and type 2 diabetes. Thereby, our findings highlight the metabolic relevance of chronobiological sleep timing.

El ayuno intermitente y sus efectos en la salud metabólica en humanos / Intermittent fasting and human metabolic health

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

When should I eat: A circadian view on food intake and metabolic regulation.

The circadian clock is a hierarchical timing system regulating most physiological and behavioral functions with a period of approximately 24 h in humans and other mammalian species. The circadian clock drives daily eating rhythms that, in turn, reinforce the circadian clock network itself to anticipate and orchestrate metabolic responses to food intake. Eating is tightly interconnected with the circadian clock and recent evidence shows that the timing of meals is crucial for the control of appetite and metabolic regulation. Obesity results from combined long-term dysregulation in food intake (homeostatic and hedonic circuits), energy expenditure, and energy storage. Increasing evidence supports that the loss of synchrony of daily rhythms significantly impairs metabolic homeostasis and is associated with obesity. This review presents an overview of mechanisms regulating food intake (homeostatic/hedonic) and focuses on the crucial role of the circadian clock on the metabolic response to eating, thus providing a fundamental research axis to maintain a healthy eating behavior.

A single night of moderate at-home sleep restriction increases hunger and food intake in overweight young adults.

OBJECTIVES: Experimental studies under laboratory conditions have shown a close link between acute sleep restriction and metabolic disorders. The aim of this study was to assess the effect of a single night of moderate sleep restriction implemented under ambulatory settings on sleep organization, food intake, blood pressure, and heart rate in overweight young adults. METHODS: In a non-randomized experimental study, we evaluated 15 young, overweight adults (mean age [± SEM] 20.8 ± 0.6 y) with a mean body mass index (BMI) 27.5 ± 6.2 kg/m2 (BMI range 18.9-36.6 kg/m2). Each participant was recorded at home during two successive nights under: 1) Regular sleep routine (from 2330 to 0730 h, 'night1') and 2) Restricted sleep (6 h in bed, from 0300 to 0900 h, "night2"). Sleep was assessed by a non-invasive mobile system (Watch-PAT200) placed on the non-dominant wrist, measuring peripheral arterial tonometry. We measured sleep duration, rapid eye movement sleep (REM), light sleep (LS), deep sleep (DS), and waking. Starting 2 d before night1, four consecutive food records assessed daily food intake. Preceding and succeeding each night, hunger/satiety feelings (measured by self-reported visual analog scales), blood pressure, and heart rate were also evaluated. RESULTS: Total sleep time was reduced in night2 (P = 0.007), with higher DS percentage (P = 0.03). Sleep onset and REM sleep latencies, LS time, and the number of wake episodes did not differ between nights. Energy intake was increased the day after night2 (P = 0.007), with increased fat and protein intakes (both P < 0.01) and feelings of hunger (P = 0.002). Systolic blood pressure was higher and heart rate faster in the morning after night2 (both P < 0.05). CONCLUSIONS: An acute moderate at-home sleep restriction exacerbated food intake and feelings of hunger, and impaired blood pressure and heart rate regulation in young, overweight adults.

Metabolic Status Modulates Choroidal Thickness - A Possible Early Indicator for Diabetic Eye Complications?

OBJECTIVE: To investigate the impact of metabolic status on choroidal thickness (ChT) in healthy subjects, patients with obesity, and type 2 diabetes. DESIGN AND METHODS: Fasting blood glucose, insulin, insulin-like growth factor-1 (IGF-1), and ChT measured by optical coherence tomography were assessed in healthy normal-weight (n=17), obese participants (n=20), and obese participants with T2D (n=16). RESULTS: ChT increased in obese participants and obese participants with T2D as compared to healthy normal-weight participants (P<0.0001). A negative correlation was observed between IGF1 and ChT (r=-0.268, P=0.050) for all cohorts. Furthermore, body mass index (BMI; R2=0.209; P=0.002; beta=0.388) and model assessment-estimated insulin resistance (HOMA-IR; R2=0.074; P=0.015; beta=0.305) were independent variables of ChT, explaining 20.9 and 7.4% of its variance (both p<0.016), whereas age, sex, and IGF-1 were not significant confounders of ChT (p>0.975). CONCLUSION: ChT is associated with metabolic characteristics, i. e., BMI and HOMA-IR. Due to the key role of choroidal function in retinal physiology, future studies are needed to evaluate whether metabolic traits, ChT, and potential metabolic eye complications are mechanistically linked.

Meal timing across the day modulates daily energy intake in adult patients with type 2 diabetes.

BACKGROUND/OBJECTIVES: We assessed the association between the timing of meals across the day with diet composition and metabolic parameters in patients with type-2 diabetes (T2D). SUBJECTS/METHODS: Eighty adults (55.2 ± 6.8 years, 45% males) patients with T2D (without insulin therapy) were included. Three non-consecutive dietary records assessed food intake. The onset time of each consumed meal/beverage was identified and assigned to one of three periods of the day: Period 1 (P1, 06:00-11:59 h), Period 2 (P2, 12:00-17:59 h), and Period 3 (P3, 18:00-00:30 h). RESULTS: Energy intake in P1 was lower compared to P2 and P3 (22.8 ± 7.9%, 37.5 ± 9.6%, and 39.7 ± 9.9%, respectively, P < 0.001). The same pattern was found for both total protein and fat intake, but carbohydrate intake was similar among periods. Patients with greater daily energy intake (as % of total energy) in P3 showed increased total food consumption, total energy, protein, and fat intake (all P < 0.05). The opposite pattern was observed in patients with greater daily energy intake in P1 (all P < 0.05). Regression analysis showed that daily energy intake was significantly reduced when a higher proportion of carbohydrates was eaten in P1 (vs. P3, P < 0.04). CONCLUSION: Increased energy intake late during the day is related to increased total food and daily energy intake in patients with T2D. A greater proportion of total carbohydrates eaten early during the day relates to lower total energy intake. Our results suggest that earlier food intake may be a nutritional tool for dietary and metabolic control in these patients.

Evaluación de modelos matemáticos para estimar el peso y talla en pacientes adultos usando CRM, RMSE, Pearson y Bland Altman / Assessment of mathematical models to estimate weight and height in adultpatients using CRM, RMSE, Pearson and Bland Altman

Introducción: La disponibilidad de datos antropométricos(peso y talla) de pacientes con poca o nula movilidad son importantes en el tratamiento médico y nutricional, para estimaresos valores se han usado modelos matemáticos que reproducen con mayor fidelidad, por lo que es importante evaluarel método de estimación de los modelos.Objetivo: Evaluar los modelos matemáticos de Rabito,Chumlea y HNHU para estimar peso y talla en pacientes adultos usando los métodos de ERM, RMSE, Pearson y Bland Altman. Materiales y métodos: Se considera los datos de 31 pacientes entre 20 y 65 años. Los datos fueron altura de rodilla(AR), circunferencia de brazo (CB), circunferencia abdominal(CA), circunferencia de la pantorrilla (CP), media brazada(MB) y envergadura de brazo (EB) comprendidos en ocho modelos de Rabito para estimar peso y talla, cuatro del HospitalNacional Hipólito Unanue (HNHU) y cuatro de Chumlea. Lacalidad de la estimación fue evaluada por los métodos de Correlación de Pearson, Error Relativo Medio (ERM), RaizCuadrado Medio del Error (RMSE) y Bland Altman. El nivel deasociación entre los métodos fue determinado por Pearson. Los cálculos fueron desarrollados usando el software estadístico R 4.1.0. Resultados: Las mediciones por el método de Pearsonpresenta una variación de 54%, el método ERM de 26.65%,por Bland Altman de 8.49% y RMSE 6.1%. Los métodos deRMSE y Bland Altman presentan una asociación de 0.72. Losmodelos de Rabito 3M (RMSE=4.38) y Rabito 3F(RMSE=4.36) reproducen los valores de peso con mayor fidelidad y para la estimación de la talla los modelos de Rabito 2M(RMSE=3.64) y Rabito 2F (RMSE = 3.82). Conclusiones: Los métodos RMSE y de Bland Altman tienen buena asociación, presentando buena estabilidad en lasevaluaciones. Los modelos matemáticos de Rabito tienenbuena estimación para peso y talla.(AU)

Introduction: The availability of anthropometric data(weight and height) of patients with little or no mobility areimportant for medical and nutritional treatment, to estimatethese values mathematical models that reproduce withgreater fidelity have been used, so it is important to evaluatethe model estimation method. Objective: To Assess the mathematical models of Rabito, Chumlea and HNHU to estimate weight and height in adul patients using the ERM, RMSE, Pearson and Bland Altmanmethods.Materials and methods: Data from 31 patients between20 and 65 years old are considered. The data were kneeheight (RA), arm circumference (AB), abdominal circumference (AC), calf circumference (CP), mean arm length (MB),and arm span (EB) comprised of eight Rabito models for estimate weight and height, four from Hospital Nacional HipólitoUnanue (HNHU) and four from Chumlea. The quality of theestimation was evaluated by the Pearson Correlation, Relative Mean Error (ERM), Root Mean Square Error (RMSE) and Bland Altman methods. The level of association between the methods was determined by Pearson. Calculations were developedusing R 4.1.0 statistical software. Results: The measurements by the Pearson method present a variation of 54%, the ERM method of 26.65%, by BlandAltman of 8.49% and RMSE 6.1%. The RMSE and Bland Altman methods present an association of 0.72. The Rabito3M (RMSE=4.38) and Rabito 3F (RMSE=4.36) models reproduce the weight values with greater fidelity and for height estimation the Rabito 2M (RMSE=3.64) and Rabito 2F (RMSE =3.82) models. Conclusions: The RMSE and Bland Altman methods havea good association, presenting good stability in the evaluations. Rabito’s mathematical models have good estimates forweight and height.(AU)

Meal Timing and Macronutrient Composition Modulate Human Metabolism and Reward-Related Drive to Eat.

The 'time-of-day' modifies the metabolic response to meals, but less data exist on the diurnal variations in the hedonic drive to eat. In the present paper, we evaluate the effects of meal timing and macronutrient composition on metabolic responses and the homeostatic vs. hedonic regulation of appetite. In study 1, 84 young, healthy adults completed an online computer-based task assessing the homeostatic and hedonic drive to eat in the morning and evening. In study 2, 24 healthy, young men received 2 identical (850 kcal each) meals in the morning (8:45 h) and evening (18:00 h), of 2 experimental conditions: (i) regular carbohydrate (CH) meals (regular-CH), and (ii) high carbohydrate (high-CH) meals, containing 50 and 80% of energy from CHs, respectively. Serial blood samples were obtained, and the postprandial feelings of hunger, satiety, wanting and liking were assessed. Study 1 revealed a higher hedonic drive to eat in the evening compared to the morning. Study 2 confirmed this diurnal pattern of hedonic appetite regulation and, moreover, showed increased glucose and insulin responses to the evening meal. Postprandial ghrelin and leptin as well as feelings of hunger and satiety were not different between the mealtimes nor between the macronutrient conditions. In line with this, the homeostatic drive to eat was neither affected by the mealtime nor macronutrient composition. Increased the hedonic drive to eat in the evening may represent a vulnerability to palatable food and, thus, energy overconsumption. Together with lower evening glucose tolerance, these findings reflect an adverse metabolic constellation at the end of the day, especially after the ingestion of CH-rich foods.

Reduced n-3 and n-6 PUFA (DHA and AA) Concentrations in Breast Milk and Erythrocytes Phospholipids during Pregnancy and Lactation in Women with Obesity.

Obesity during pregnancy is a worrying public health problem worldwide. Maternal diet is critical for fatty acid (FA) placental transport and FA content in breast milk (BM). We evaluated FA composition in erythrocytes phospholipids (EP) and BM in pregnant women with (OBE, n = 30) and without (non-OBE, n = 31) obesity. Sixty-one healthy women were evaluated at their 20-24th gestational week and followed until 6th month of lactation. Diet was evaluated through a food frequency questionnaire. FA composition of EP and BM was assessed by gas-liquid chromatography. The OBE group showed lower diet quality, but total n-6 and n-3 polyunsaturated FA (PUFA), ALA, EPA, and DHA dietary intake was similar between groups. N-3 PUFA, ALA, DHA, and the n-6/n-3 PUFA ratio in EP were lower at the 6th lactation month in the OBE group. In BM, the arachidonic acid (AA) concentration was lower at the end of the lactation, and DHA content showed an earlier and constant decline in the OBE group compared to the non-OBE group. In conclusion, n-3 PUFA and AA and DHA levels were reduced in EP and BM in pregnant women with obesity. Strategies to increase n-3 PUFA are urgently needed during pregnancy and lactation, particularly in women with obesity.

Acute mild dim light at night slightly modifies sleep but does not affect glucose homeostasis in healthy men.

OBJECTIVE: We evaluated the effect of acute mild light exposure at night on sleep architecture and glucose homeostasis. PATIENTS/METHODS: Twenty healthy normal-weight men took part in two conditions of a randomized, controlled, balanced cross-over experimental study: i) two-consecutive nights with 8-h of sleep under dLAN (<5 lux) or ii) total darkness (CON). Sleep was evaluated by polysomnography. In the morning following 'night2', glucose homeostasis was assessed by an intravenous glucose tolerance test (ivGTT) with consecutive measures of glucose, insulin, and c-peptide. Plasma cortisol was measured at night before sleep, after morning awakening, and during mid-afternoon hours. RESULTS: There was no significant difference in total sleep time, sleep efficiency, and sleep latency between conditions (all p > 0.66). However, NREM sleep stage N3 latency was prolonged after dLAN (p = 0.02) and NREM sleep stage 2 was decreased after two nights with dLAN (p = 0.04). During the first sleep hour, power in slow-oscillations, slow-waves, and delta bands diminished after dLAN (all p < 0.04). Glucose, insulin, and c-peptide were not altered by dLAN (all p > 0.14). Cortisol was reduced in the afternoon after 'night1' and in the morning after 'night2' (both p < 0.03). CONCLUSIONS: dLAN slightly disturbed sleep architecture and quality without impairment of glucose homeostasis. Longer exposure to chronic dLAN might be needed to unmask its hypothesized metabolic consequences.

Impact of Shift Work on the Eating Pattern, Physical Activity and Daytime Sleepiness Among Chilean Healthcare Workers.

We evaluated the eating pattern, physical activity, and daytime sleepiness level in Chilean shift workers. Fifty, middle-aged adult health workers from a public hospital in Santiago, Chile, were included: a group undergoing shift work (shift workers, including at least one "night shift" and one "long day", n = 33), and day workers under traditional schedule (from 8:00 to 17:00h, n = 17). Body composition, physical activity, and daytime sleepiness levels, and diet characteristics (diet composition, meals' timing, and diet quality) were assessed. Despite similar total energy intake, shift worker showed lower carbohydrate (% of energy) and higher protein intake (both P < 0.01), decreased diet quality, an irregular eating pattern, and delayed meal timing (all P < 0.05). Physical activity and daytime sleepiness levels did not differ between groups. Findings from this first Chilean study in healthcare shift workers support the fact that meal timing and diet quality appear as critical factors for upcoming intervention studies in this group.

Diet, Plasma, Erythrocytes, and Spermatozoa Fatty Acid Composition Changes in Young Vegan Men.

There has been increasing interest in vegan diets, but how this dietary pattern regulates tissue fatty acids (FA), especially in men, is unclear. Our aim was to evaluate the effect of a vegan diet on plasma, erythrocyte, and spermatozoa FA composition in young men. Two groups consisting of 67 young (18-25 years old) men were studied. One group following an omnivore diet but did not consume fish, shellfish or other marine foods (control, n = 33), and another group following a vegan diet (vegan, n = 34) for at least 12 months were compared. Dietary intake was assessed via a food frequency questionnaire and a 24-h recall. FA composition was measured in plasma, erythrocyte phospholipids, and spermatozoa by gas-liquid chromatography. Compared to controls, the vegan group had higher reported intakes of carbohydrate, dietary fiber, vitamins (C, E, K, and folate), and minerals (copper, potassium) but lower intakes of cholesterol, trans FA, vitamins B6 , D, and B12 , and minerals (calcium, iron, and zinc). Vegan's reported a lower saturated FA and not arachidonic acid intake, both groups did not intake eicosapentaenoic acid and docosahexaenoic acid (DHA), but vegan's showed a higher alpha linolenic acid ALA intake. Vegans had higher plasma, erythrocyte phospholipid, and spermatozoa ALA, but lower levels of other n-3 polyunsaturated fatty acid (PUFA), especially DHA. Vegans were characterized by higher ALA, but lower levels of other n-3 PUFA, especially DHA in plasma, erythrocytes, and spermatozoids. The biological significance of these findings requires further study.

Chronobiological aspects of sleep restriction modulate subsequent spontaneous physical activity.

PURPOSE: First evidence suggests that chronobiological aspects of sleep restriction affect metabolic conditions. Our aim was to investigate whether spontaneous free-living physical activity likewise is affected by chronobiological timing of short sleep. METHODS: In an experimental randomized, balanced cross-over design, eleven healthy, normal-weight (BMI: 23.9 ± 0.4 kg/m2) men were evaluated. Physical activity was assessed by tri-axial wrist actigraphy after (i) four-hour sleep during the first night-half of the night ('late night sleep loss'), (ii) four-hour sleep during the second night-half ('early night sleep loss'), and (iii) eight-hour regular sleep ('regular sleep'), from 7:00 to 24:00 (17 h). Feelings of tiredness and activity were measured by semi-quantitative questionnaires. RESULTS: Physical activity differed between sleep conditions (P < 0.05) with the lowest physical activity after 'late night sleep loss'. Accordingly, less time was spent in high-intensity physical activity after 'late night sleep loss' as compared to the 'early night sleep loss' and 'regular sleep' conditions (both P < 0.05). Perceived feelings of tiredness were higher after both short sleep conditions as compared to 'regular sleep' (both P < 0.05). CONCLUSIONS: Sleep restriction during the second half of the night elicits stronger effects on spontaneous physical activity than sleep restriction during the first half of the night despite identical sleep duration, but the impact of longer period awake needs to be evaluated in further research. In sum, these data indicate that not only short sleep per se but also chronobiological aspects modulate physical activity pattern.

Night-time cardiac autonomic modulation as a function of sleep-wake stages is modified in otherwise healthy overweight adolescents.

OBJECTIVE: Even though sympathetic dominance during the daytime period is well known, currently, scarce data exist on autonomic nervous system (ANS) regulation during sleep in pediatric obesity. We aimed to evaluate sleep cardiac ANS regulation in normal-weight (NW) and overweight and obese (OW) adolescents. PATIENTS/METHODS: In this study, 60 healthy adolescents (15.7 ± 0.7 years) belonging to a birth cohort since infancy were classified based on body mass index percentiles criteria as: OW (N = 27) or NW (N = 33). Sleep was evaluated by polysomnography (PSG) during two consecutive in-lab overnight sessions. Non-rapid eye movement (non-REM) sleep stages (stages 1, 2, and slow-wave sleep [SWS]), rapid eye movement (REM) sleep, and wakefulness (Wake) were scored. R-waves were detected automatically in the electrocardiographic (ECG) signal. An all-night heart rate variability analysis was conducted in the ECG signal, with several time- and frequency-domain measures calculated for each sleep-wake stage. Sleep time was divided into thirds (T1, T2, T3). The analysis was performed using a mixed-effects linear regression model. RESULTS: Sleep organization was comparable except for reduced REM sleep percentage in the OW group (p < 0.04). Shorter R-R intervals were found for all sleep stages in the OW group; time-domain measured standard deviation of all R-R intervals (RRSD) was lower during stage 2, SWS and REM sleep (all p < 0.05). The square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD) was also lower only during wake after sleep onset (WASO) in T1 and T3 (p < 0.05). The OW group had increased very low- and low-frequency (LF) power during WASO (in T1 and T2), and LF power during stage 2 and REM sleep (in T2). During WASO in the OW group, high-frequency (HF) power was lower (in T1 and T2), and LF/HF ratio was higher (in T2, p < 0.007). CONCLUSIONS: Several sleep-stage-dependent changes in cardiac autonomic regulation characterized the OW group. As sleep-related ANS balance was disturbed in the absence of concomitant metabolic alterations in this sample of otherwise healthy OW adolescents, their relevance for pediatric obesity should be further explored throughout development.

Timing Modulates the Effect of Sleep Loss on Glucose Homeostasis.

CONTEXT: Chronobiological factors may modulate the impact of sleep loss on glucose homeostasis. However, these interactions have not been systematically assessed in humans. OBJECTIVE: To assess the effect of sleep loss during the late vs early night on glucose homeostasis. DESIGN: Fifteen normal-weight men participated in three conditions of a randomized, balanced crossover study comprising two conditions with shortened sleep (i.e., 4 hours of sleep during the first or the second half of the night) and a control condition with 8 hours of sleep. Glucose, insulin, cortisol, and glucagon were measured. Insulin sensitivity and secretion were assessed with a Botnia clamp. RESULTS: Compared with regular sleep duration, sleep loss reduced insulin sensitivity (M-value; P = 0.031) irrespective of early- or late-night timing (P = 0.691). The disposition index (i.e., the ß-cell response adjusted for insulin sensitivity) also tended to be impaired by short sleep (P = 0.056) but not by sleep timing (P = 0.543). In contrast, sleep loss in the second half but not the first half of the night induced reductions in morning glucagon and cortisol levels (P < 0.031) followed by a transient increase in cortisol (P < 0.044). CONCLUSIONS: Although sleep deprivation acutely reduced insulin sensitivity irrespective of its nocturnal timing, sleep loss in the early morning compromised α-cell and hypothalamic-pituitary-adrenal axis activity to a greater extent than sleep loss in the first half of the night. This pattern suggests that the timing of sleep restriction can partly potentiate its deleterious metabolic effects.

Sleep Loss Disrupts Morning-to-Evening Differences in Human White Adipose Tissue Transcriptome.

CONTEXT: Chronodisruption, as caused by such conditions as perturbations of 24-hour rhythms of physiology and behavior, may promote the development of metabolic diseases. OBJECTIVE: To assess the acute effects of sleep curtailment on circadian regulation (i.e., morning-to-evening differences) of white adipose tissue (WAT) transcriptome in normal-weight men. DESIGN: Fifteen healthy men aged 18 to 30 years (mean ± SEM, 24.0 ± 0.9years) were studied. In randomized, balanced order they underwent three separate nights with regular sleep duration (8 hours of sleep between 11:00 pm and 7:00 am), sleep restriction (4 hours of sleep between 3:00 am and 7:00 am), and sleep deprivation (no sleep at all). Sleep was polysomnographically evaluated. WAT biopsy samples were taken twice at 9:00 pm and 7:00 am to assess morning-to-evening differences. WAT transcriptome profile was assessed by RNA sequencing, and expression of relevant circadian core clock genes were analyzed. Glucose homeostasis, lipid profile, and adipokines were assessed. RESULTS: Sleep restriction dramatically blunted morning-to-evening transcriptome variations with further dampening after sleep deprivation. Although most core clock genes remained stably rhythmic, morning-to-evening regulated pathways of carbohydrate and lipid metabolism were highly sensitive to sleep loss. In particular, genes associated with carbohydrate breakdown lost rhythmicity after sleep deprivation, with an overall trend toward an upregulation in the morning. In line with specific transcriptional changes in WAT, retinol-binding-protein 4 was increased and ß-cell secretory capacity was diminished. CONCLUSIONS: Acute sleep loss induces a profound restructuring of morning-to-evening WAT transcriptome with uncoupling from the local clock machinery, resulting in increased WAT carbohydrate turnover and impaired glucose homeostasis. Our data support an optimization of sleep duration and timing to prevent metabolic disorders such as obesity and type 2 diabetes.